Dancing with disorder: chorea - an unusual and neglected manifestation of antiphospholipid syndrome.

OBJECTIVES: Chorea, characterised by involuntary, irregular movements, is a rare neurological manifestation of antiphospholipid syndrome (APS). The specific clinical features remain unclear. This study aimed to summarise the available evidence on antiphospholipid antibody (aPL)-associated chorea. METHODS: We used a mixed-methods approach, combining data from patients with chorea with aPL positivity admitted to Peking Union Medical College Hospital (PUMCH) from 2014 to 2024, with cases identified in public databases since 1983. We collected and analysed clinical, laboratory, and imaging results, along with their treatments and outcomes. RESULTS: A total of 180 patients with incident aPL-associated chorea were included (13 from PUMCH and 167 from the literature). The majority (81.7%) were female, with a mean age of chorea onset 22.8 years (SD=16.0). Chorea was the initial symptom in 87.9% of cases and often occurred as a single episode (67%), involving bilateral limbs (58.8%) and both upper and lower limbs (87.2%). 43.3% met the 2023 American College of Rheumatology (ACR)/European Alliance of Associations for Rheumatology (EULAR) APS classification criteria. Thrombocytopenia (30.0%) and arterial thrombosis (29.1%) were the most common manifestations. Lupus anticoagulant was positive in 84.2% of patients, anticardiolipin IgG in 70.8%, and anti-ß2 glycoprotein I IgG in 52.9%. Among those who had results available for the three tests, 57.6% were triple-positive. ANAs were positive in 63.6%. MRI revealed basal ganglia lesions in only 14.8% of patients, whereas all positron emission tomography (PET) scans showed contralateral striatal hypermetabolism. Treatment varied, with most receiving combination therapies of neuroleptics, anticoagulants, antiplatelets, steroids and immunosuppressants. Chorea completely or partially improved in 95.5% of patients. CONCLUSION: Chorea is a significant but under-recognised manifestation of APS, predominantly affecting young women and often presenting as the initial symptom. Characteristic PET findings of contralateral striatal hypermetabolism can assist in diagnosis. Treatments with glucocorticoids and immunosuppressive therapies appear beneficial. Further research is needed to understand the pathophysiology and optimise management strategies for aPL-associated chorea.

Predicting the risk of cardiovascular and cerebrovascular event in systemic lupus erythematosus: a Chinese SLE treatment and research group study XXVI.

OBJECTIVE: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular and cerebrovascular events (CCEs). Furthermore, CCE was a significant factor contributing to mortality in patients with SLE. However, no clinical model exists that can predict which patients are at high risk. The purpose of this study was to develop a practical model for predicting the risk of CCE in people with SLE. METHODS: This study was based on the Chinese SLE Treatment and Research Group cohort. A total of 2399 patients, who had a follow-up period of over 3 years and were diagnosed with SLE for less than 1 year at the start of the study, were included. Cox proportional hazards regression and least absolute shrinkage and selection operator regression were used to establish the model. Internal validation was performed, and the predictive power of the model was evaluated. RESULTS: During the follow-up period, 93 patients had CCEs. The prediction model included nine variables: male gender, smoking, hypertension, age of SLE onset >40, cutaneous involvement, arthritis, anti-ß2GP1 antibody positivity, high-dose glucocorticoids and hydroxychloroquine usage. The model's C index was 0.801. Patients with a prognostic index over 0.544 were classified into the high-risk group. CONCLUSION: We have developed a predictive model that uses clinical indicators to assess the probability of CCE in patients diagnosed with SLE. This model has the ability to precisely predict the risk of CCE in patients with SLE. We recommended using this model in the routine assessment of patients with SLE.

Incidence and prevalence of systemic lupus erythematosus in urban China, 2013-2017: A nationwide population-based study.

Systemic lupus erythematosus (SLE) is becoming a growing public health concern due to increasing disease and economic burdens. Epidemiological information about SLE, especially its incidence rate, is limited in developing countries. In the current study, we sought to investigate the incidence, prevalence, and economic burdens of SLE in urban China. We conducted a nationwide population-based cohort study using databases from Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance between 2013 and 2017, covering approximately 300 million residents in 23 provincial regions in China. Incidence rate and prevalence were standardized by age and gender to China's 2010 national census data. Additionally, we calculated the average annual costs and hospital visit rates. A total of 132,258 SLE patients were identified during the study period, with a mean age of 43.03 years (standard deviation: 15.29 years). Of these patients, 81.33% were women. In 2017, the standardized incidence rate of SLE in China was 14.09 (95% confidence interval (CI), 11.95-16.41) per 100,000 person-years, with a higher incidence in women than in men (26.41 vs. 5.92 per 100,000 person-years). Standardized prevalence in 2017 was 47.61 (41.77-53.83), 94.16 (80.67-108.69), and 17.86 (13.84-22.38) per 100,000 people in the overall, female, and male populations, respectively. The average annual rates of increase in prevalence were 21.50%, 19.72%, and 25.67% from 2013 to 2017 in the overall, female, and male populations, respectively. The age-specific incidence rates peaked at 30-49 years old in women and 40-59 years old in men. SLE incident and prevalent cases were most common in North-West China and less common in southern and eastern China. Distinct variations in incidence rates across different regions are also consistent with the varying levels of ultraviolet radiation exposure in China. Additionally, the average estimated annual per-capita cost was 1599.34 US dollars in SLE patients, with the highest costs observed in adolescent and young adult patients among different age groups. The SLE population in China is rapidly expanding, and younger at onset, especially in women, which has placed significant burdens on China's healthcare system.

Identification of Lupus-Associated Genes in the Pathogenesis of Pre-eclampsia Via Bioinformatic Analysis.

Pre-eclampsia (PE) is a severe pregnancy complication that is more common in patients with systemic lupus erythematosus (SLE). Although the exact causes of these conditions are not fully understood, the immune system plays a key role. To investigate the connection between SLE and PE, we analyzed genes associated with SLE that may contribute to the development of PE. We collected 9 microarray data sets from the NCBI GEO database and used Limma to identify the differentially expressed genes (DEGs). In addition, we employed weighted gene co-expression network analysis (WGCNA) to pinpoint the hub genes of SLE and examined immune infiltration using Cibersort. By constructing a protein-protein interaction (PPI) network and using CytoHubba, we identified the top 20 PE hub genes. Subsequently, we created a nomogram and conducted a receiver operating characteristic (ROC) analysis to predict the risk of PE. Our analysis, including gene set enrichment analysis (GSEA) and PE DEGs enrichment analysis, revealed significant involvement in placenta development and immune response. Two pivotal genes, BCL6 and MME, were identified, and their validity was confirmed using 5 data sets. The nomogram demonstrated good diagnostic performance (AUC: 0.82-0.96). Furthermore, we found elevated expression levels of both genes in SLE peripheral blood mononuclear cells (PBMCs) and PE placental specimens within the case group. Analysis of immune infiltration in the SLE data set showed a strong positive correlation between the expression of both genes and neutrophil infiltration. BCL6 and MME emerged as crucial genes in lupus-related pregnancies associated with the development of PE, for which we devised a nomogram. These findings provide potential candidate genes for further research in the diagnosis and understanding of the pathophysiology of PE.

Phenotypic subgroup in serologically active clinically quiescent systemic lupus erythematosus: A cluster analysis based on CSTAR cohort.

BACKGROUND: Serologically active clinically quiescent (SACQ) is a state within systemic lupus erythematosus (SLE) characterized by elevated serologic markers without clinical activity. The heterogeneity in SACQ patients poses challenges in disease management. This multicenter prospective study aimed to identify distinct SACQ subgroups and assess their utility in predicting organ damage. METHODS: SACQ was defined as a sustained period of at least 6 months with persistent serologic activity, marked by positive anti-double-stranded DNA (dsDNA) antibodies and/or hypocomplementemia, and without clinical activity. Cluster analysis was employed, utilizing 16 independent components to delineate phenotypes. FINDINGS: Among the 4,107 patients with SLE, 990 (24.1%) achieved SACQ within 2.0 ± 2.3 years on average. Over a total follow-up of 7,105.1 patient years, 340 (34.3%) experienced flares, and 134 (13.5%) developed organ damage. Three distinct SACQ subgroups were identified. Cluster 1 (n = 219, 22.1%) consisted predominantly of elderly males with a history of major organ involvement at SLE diagnosis, showing the highest risk of severe flares (16.4%) and organ damage (27.9%). Cluster 2 (n = 279, 28.2%) was characterized by milder disease and a lower risk of damage accrual (5.7%). Notably, 86 patients (30.8%) in cluster 2 successfully discontinued low-dose glucocorticoids, with 49 of them doing so without experiencing flares. Cluster 3 (n = 492, 49.7%) featured the highest proportion of lupus nephritis and a moderate risk of organ damage (11.8%), with male patients showing significantly higher risk of damage (hazard ratio [HR] = 4.51, 95% confidence interval [CI], 1.82-11.79). CONCLUSION: This study identified three distinct SACQ clusters, each with specific prognostic implications. This classification could enhance personalized management for SACQ patients. FUNDING: This work was funded by the National Key R&D Program (2021YFC2501300), the Beijing Municipal Science & Technology Commission (Z201100005520023), the CAMS Innovation Fund (2021-I2M-1-005), and National High-Level Hospital Clinical Research Funding (2022-PUMCH-D-009).

Single-cell RNA sequencing of peripheral blood mononuclear cells from pregnant women with Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease. Furthermore, SLE women have an increased likelihood of encountering adverse pregnancy outcomes such as diabetes and hypertension. The etiology of SLE involves a multifaceted interplay of genetic, immune, endocrine, and environmental factors, which contributes to a breakdown in the immune system's tolerance to self-antigens. Recent studies have highlighted a strong correlation between the severity of renal involvement in lupus nephritis and B cell dysfunction in patients, as elucidated through single-cell transcriptomics. Additionally, comparative studies have revealed notable differences in the immune cell profile between pregnant women with lupus and healthy pregnant women. A key observation the marked reduction in the proportion of CD4+ T cells in pregnant women suffering from lupus. Despite these findings, the detailed transcriptomic alterations within high-resolution immune cell profiling during activate phase of SLE in pregnancy remain inadequately understood. In our study, we focused on comparing the transcriptomic expression patterns of peripheral blood immune cells between pregnant women with active SLE and those with stable SLE. Our data confirmed significant differences in IFN signaling and pregnancy-related factors in T cells, NK cells, B cells, and macrophages, contrasting the immune cells of pregnant women with active SLE against those with stable SLE. Additionally, the proportion of CD56+ NK cells was significantly increased in pregnant women with SLE. The correlation between the transcriptomic profiles of immune cells and the activity of SLE during pregnancy may provide potential strategies for predicting and treating SLE during pregnancy.

Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles.

BACKGROUND: Cell-free long RNAs in human plasma and extracellular vesicles (EVs) have shown promise as biomarkers in liquid biopsy, despite their fragmented nature. METHODS: To investigate these fragmented cell-free RNAs (cfRNAs), we developed a cost-effective cfRNA sequencing method called DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing). DETECTOR-seq utilised a meticulously tailored set of customised guide RNAs to remove large amounts of unwanted RNAs (i.e., fragmented ribosomal and mitochondrial RNAs) in human plasma. Early barcoding strategy was implemented to reduce costs and minimise plasma requirements. RESULTS: Using DETECTOR-seq, we conducted a comprehensive analysis of cell-free transcriptomes in both whole human plasma and EVs. Our analysis revealed discernible distributions of RNA types in plasma and EVs. Plasma exhibited pronounced enrichment in structured circular RNAs, tRNAs, Y RNAs and viral RNAs, while EVs showed enrichment in messenger RNAs (mRNAs) and signal recognition particle RNAs (srpRNAs). Functional pathway analysis highlighted RNA splicing-related ribonucleoproteins (RNPs) and antimicrobial humoral response genes in plasma, while EVs demonstrated enrichment in transcriptional activity, cell migration and antigen receptor-mediated immune signals. Our study indicates the comparable potential of cfRNAs from whole plasma and EVs in distinguishing cancer patients (i.e., colorectal and lung cancer) from healthy donors. And microbial cfRNAs in plasma showed potential in classifying specific cancer types. CONCLUSIONS: Our comprehensive analysis of total and EV cfRNAs in paired plasma samples provides valuable insights for determining the need for EV purification in cfRNA-based studies. We envision the cost effectiveness and efficiency of DETECTOR-seq will empower transcriptome-wide investigations in the fields of cfRNAs and liquid biopsy. KEYPOINTS: DETECTOR-seq (depletion-assisted multiplexed cell-free total RNA sequencing) enabled efficient and specific depletion of sequences derived from fragmented ribosomal and mitochondrial RNAs in plasma. Distinct human and microbial cell-free RNA (cfRNA) signatures in whole Plasma versus extracellular vesicles (EVs) were revealed. Both Plasma and EV cfRNAs were capable of distinguishing cancer patients from normal individuals, while microbial RNAs in Plasma cfRNAs enabled better classification of cancer types than EV cfRNAs.

Predictive Factors for the Common Adverse Maternal and Fetal Outcomes in Pregnancies Complicated by Systemic Lupus Erythematosus.

Objectives: This study aimed to evaluate the outcomes of pregnancy in patients with systemic lupus erythematosus (SLE). It focused on identifying clinical and laboratory markers that could predict the common adverse pregnancy outcomes (APOs) after 20 weeks of gestation, namely preeclampsia (PE) and preterm birth (PTB) in them. Methods: Pregnant SLE women who delivered at the study center from 2010 to 2023 were retrospectively analyzed. Categorical variables were evaluated using the chi-square test or Fisher's exact test, while continuous variables underwent Mann-Whitney U testing. Stepwise regression was used to assess the predictors of pregnancy outcomes. Results: The study enrolled 445 pregnancies in 408 women diagnosed with SLE. Of these, 202 pregnancies (45.4%) resulted in at least one APO. Disease flare-ups, hypertension, and proteinuria during the first trimester were primary predictors of at least one APO and PTB. The most frequently recorded maternal adverse outcome was PE (14.6%), while PTB accounted for 32.6% of fetal adverse outcomes. Multivariate regression analysis identified hypertension, history of PE, associated antiphospholipid syndrome (APS), proteinuria, and low serum C4 in the first trimester as independent risk factors for PE. Regular follow-ups at our center correlated with lower risks of APOs, PE, and PTB. APS also emerged as a risk factor for PTB, whereas the use of hydroxychloroquine (HCQ) during pregnancy seemed to protect against PTB. Conclusion: For pregnancies complicated by SLE, we recommend early pregnancy screening for proteinuria-even in the absence of lupus nephritis-as well as continued use of HCQ and routine prenatal care throughout pregnancy.

Impact of antiphospholipid antibodies on cardiac valve lesions in systemic lupus erythematosus: a systematic review and meta-analysis.

This meta-analysis assesses antiphospholipid antibodies' (aPLs) impact on heart valve disease in Systemic Lupus Erythematosus (SLE) patients. We searched PubMed, Embase, Cochrane, and Web of Science up to January 2024 for comparative studies of heart valve disease in aPL-positive versus aPL-negative SLE patients. Fixed-effect or random-effect models were used to synthesize data, with I2 and sensitivity analyses for heterogeneity and the trim-and-fill method for publication bias. Including 25 studies with 8089 patients, of which 919 had valvular changes, aPLs significantly increased the risk of heart valve disease (OR = 2.24, 95% CI: 1.58-3.18, p < 0.001). Lupus anticoagulant (LA) indicated the highest risk (OR = 4.90, 95% CI: 2.26-10.60, p < 0.001), anticardiolipin antibodies (aCL) doubled the risk (OR = 2.69, 95% CI: 1.47-4.93, p = 0.001), and anti-ß2 glycoprotein I (aß2GPI) showed a 70% increase (OR = 1.70, 95% CI: 1.17-2.45, p = 0.005). Valve-specific analysis indicated the mitral valve was most commonly involved (26.89%), with higher occurrences in aPL-positive patients (33.34% vs. 15.92%, p = 0.053). Aortic and tricuspid valve involvements were 13.11% vs. 5.42% (p = 0.147) and 12.03% vs. 8.52% (p = 0.039), respectively. Pulmonary valve disease was rare and similar across groups (1.01% in aPL-positive vs. 1.52% in aPL-negative). Significantly, only tricuspid valve disease showed increased risk in aPL-positive patients (OR = 2.66, 95% CI: 1.05-6.75, p = 0.039). APLs notably increase the risk of heart valve disease in SLE patients, with a pronounced effect on tricuspid valve involvement. Regular cardiac assessments for aPL-positive SLE patients are crucial for timely intervention and improved prognosis.

Interstitial lung diseases associated with ANCA positivity: A different disease spectrum from interstitial pneumonia with autoimmune features.

BACKGROUND: Anti-neutrophil cytoplasmic antibody (ANCA) is a type of autoantibodies associated with vasculitis. ANCA positivity is commonly observed in interstitial lung disease (ILD) patients. 7%-10% of ANCA-positive ILD patients don't present any symptoms of systemic vasculitis and are termed ANCA-positive idiopathic interstitial pneumonia (ANCA-IIP). Some researchers propose that ANCA-IIP should be categorized as interstitial pneumonia with autoimmune features (IPAF), although the official ATS/ERS statements exclude ANCA-IIP from this classification. Whether ANCA-IIP should be categorized into the entity of IPAF is still debatable. METHODS: Patients diagnosed with ANCA-IIP and those with IPAF were analyzed in a retrospective study of ILD. The clinical outcomes were determined through pulmonary function tests (PFTs) after a one-year follow-up, as well as assessing all-cause mortality. RESULTS: 27 patients with ANCA-IIP and 143 patients with IPAF were analyzed from a cohort of 995 patients with ILD. Patients in the ANCA-IIP group had an older age and a high proportion of males compared to those in the IPAF group. PFT results at baseline were similar between the two groups, except for a better FEV1% in the ANCA-IIP group. Glucocorticoid and immunosuppressive therapy improved pulmonary function in patients with IPAF, but it continued to deteriorate after one year of treatment in the ANCA-IIP group. Furthermore, the all-cause mortality rate was significantly higher in the ANCA-IIP group than in the IPAF group (22.2% vs. 6.3%, P = 0.017). CONCLUSION: The responses to glucocorticoid and immunosuppressive therapy differ between the ANCA-IIP and IPAF groups, leading to divergent prognoses. Therefore, it is inappropriate to classify ANCA-IIP as part of IPAF.

The additional role of anti-nucleosome antibodies in the prediction of renal damage in systemic lupus erythematosus based on CSTAR (XXV).

OBJECTIVES: The predominant determinant of an unfavorable prognosis among Systemic Lupus Erythematosus (SLE) patients resides in the irreversible organ damage. This prospective cohort study aimed to identify the additional value of anti-nucleosome antibodies on organ damage accumulation in SLE patients. METHODS: Based on the Chinese SLE Treatment and Research group (CSTAR) registry, demographic characteristics, autoantibodies profiles, and clinical manifestations were collected at baseline. Follow-up data were collected by reviewing clinical records. RESULTS: Of 2481 SLE patients with full follow-up data, 663 (26.7%) were anti-nucleosome antibodies positive and 1668 (68.0%) were anti-dsDNA antibodies positive. 764 (30.8%) patients developed new organ damage during a mean follow-up of 4.31 ± 2.60 years. At baseline, patients with positive anti-nucleosome antibodies have a higher rate of lupus nephritis (50.7% vs 36.2%, p < .001). According to the multivariable Cox regression analysis, both anti-nucleosome (HR = 1.30, 95% CI, 1.09-1.54, p < .001) and anti-dsDNA antibodies (HR=1.68, 95% CI, 1.38-2.05, p < .001) were associated with organ damage accumulation. Anti-nucleosome (HR = 2.51, 95% CI, 1.81-3.46, p < .001) and anti-dsDNA antibodies (HR = 1.69, 95% CI, 1.39-2.06, p < .001) were independent predictors for renal damage. Furthermore, the combination of the two antibodies can provide more accurate information about renal damage in overall SLE patients (HR = 3.19, 95% CI, 2.49-4.10, p < .001) and patients with lupus nephritis at baseline (HR = 2.86, 95% CI, 2.29-3.57, p < .001). CONCLUSION: Besides anti-dsDNA antibodies, anti-nucleosome antibodies can also provide information about organ damage accrual during follow-up. The ability of co-positivity of anti-nucleosome and anti-dsDNA antibodies in predicting renal damage may lead to additional benefits in the follow-up of these patients.

Exploring the impact of acute viral exposure on clinical characteristics and antibody profiles in antiphospholipid syndrome: a study in CAPSTONE.

The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.

The prognosis and management of reclassified systemic lupus erythematosus associated pulmonary arterial hypertension according to 2022 ESC/ERS guidelines.

BACKGROUND AND AIMS: The 2022 European Society of Cardiology/European Respiratory Society (ESC/ERS) guideline has recently revised the hemodynamic definition of pulmonary arterial hypertension. However, there is currently limited research on the prognosis and treatment of system lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) patients that have been reclassified by the new hemodynamic definition. This study aims to analyze the prognosis of newly reclassified SLE-PAH patients and provide recommendations for the management strategy. METHODS: This retrospective study analyzed records of 236 SLE-PAH patients who visited Peking Union Medical College Hospital (PUMCH) from 2011 to 2023, among whom 22 patients were reclassified into mild SLE-PAH (mean pulmonary arterial pressure (mPAP) of 21-24 mmHg, pulmonary vascular resistance (PVR) of 2-3 WU, and PAWP ≤ 15 mmHg) according to the guidelines and 14 were defined as unclassified SLE-PAH patients (mPAP 21-24 mmHg and PVR ≤ 2 WU). The prognosis was compared among mild SLE-PAH, unclassified SLE-PH, and conventional SLE-PAH patients (mPAP ≥ 25 mmHg and PVR > 3WU). Besides, the effectiveness of pulmonary arterial hypertension (PAH)-specific therapy was evaluated in mild SLE-PAH patients. RESULTS: Those mild SLE-PAH patients had significantly longer progression-free time than the conventional SLE-PAH patients. Among the mild SLE-PAH patients, 4 did not receive PAH-specific therapy and had a similar prognosis as patients not receiving specific therapy. CONCLUSIONS: This study supports the revised hemodynamic definition of SLE-PAH in the 2022 ESC/ERS guideline. Those mild and unclassified SLE-PH patients had a better prognosis, demonstrating the possibility and significance of early diagnosis and intervention for SLE-PAH. This study also proposed a hypothesis that IIT against SLE might be sufficient for those reclassified SLE-PAH patients.

Microarray analysis of microrna expression in peripheral blood mononuclear cells of patients with polymyositis and dermatomyositis.

Background and Objectives: MicroRNAs (miRNAs) represent a new class of biomarkers in the context of connective tissue disorders. The miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) of patients with polymyositis (PM) and dermatomyositis (DM) have not been fully elucidated. The objective is to investigate miRNAs expression profile in PBMCs of patients with PM/DM. Methods: Microarray technology was used to identify differentially expressed miRNAs in PBMCs obtained from 6 untreated PM/DM patients and 3 healthy controls (HCs). TaqMan-based stem-loop real-time PCR detection was used for validation in a cohort of 34 PM/DM patients and 20 HCs. Results: Microarray analysis revealed 38 differentially expressed miRNAs (24 up-regulated and 14 down-regulated) in PM/DM patients compared to HCs. Four miRNAs (miR-320a, miR-335-3p, miR-34a-5p and miR-454-3p) were chosen for real-time PCR validation. The expression of miR-34a-5p was significantly upregulated in PM/DM group (P < 0.05). In subgroup analysis, miR-34a-5p was significantly upregulated in interstitial lung disease (ILD) group and DM group (P < 0.001). The level of SIRT1, a validated target of miR-34a, was significantly lower in PBMCs of PM/DM patients compared with HCs. Conclusions: MiR-34a-5p may potentially participate in the pathogenesis of PM/DM through SIRT1, and may serve as a potential new biomarker for PM/DM-ILD.

Higher Dietary Inflammatory Index and Increased Mortality Rate of Adults With Hyperuricemia: Findings From the National Health and Nutritional Examination Survey (2001-2018).

OBJECTIVE: This study aimed to assess the association between Dietary Inflammatory Index (DII) score and death among adults with hyperuricemia. METHODS: We collected data from the 2001 to 2018 cohorts of the National Health and Nutritional Examination Survey. Death information was obtained based on death certificate records from the National Death Index through December 31, 2019. The associations between DII score and all-cause, cardiovascular disease (CVD), and cancer death were investigated by using Cox proportional hazards regression models. RESULTS: We enrolled 7,786 participants with hyperuricemia in this study. The DII score ranged from -4.42 to 4.61. Higher DII score was significantly associated with higher levels of body mass index, glycohemoglobin, glucose, low-density lipoprotein-cholesterol, and C-reactive protein (all P < 0.05). During 67,851 person-years of follow-up, deaths of 1,456 participants were identified, including 532 CVD deaths and 246 cancer deaths. After adjusting for potential variables, significant higher risk of all-cause (hazard ratio [HR] 1.18, 95% confidence interval [95% CI] 1.03-1.36, P = 0.01) and CVD (HR 1.30, 95% CI 1.03-1.63, P = 0.02) death was observed for individuals with higher DII scores. Considering the DII score as a continuous variable, the risk of all-cause and CVD death increases 5% (HR 1.05, 95% CI 1.01-1.08) and 8% (HR 1.08, 95% CI 1.02-1.15) with each one-unit increment in DII score, respectively. Subgroup analysis indicated that the association between DII score and all-cause death among participants with hyperuricemia was more significant in males. CONCLUSION: DII score is found to be positively associated with all-cause and CVD death of adults with hyperuricemia. Controlling the intake of proinflammatory food might be a potential strategy to reduce the mortality rate.

Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study.

BACKGROUND: To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP). METHODS: This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected. RESULTS: A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories. CONCLUSION: SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort.

BACKGROUND: The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. OBJECTIVES: To validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. METHODS: This was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by "expert consensus panel" served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. RESULTS: A total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. CONCLUSION: The 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.

Prediction of progressive fibrosing interstitial lung disease in patients with systemic sclerosis: insight from the CRDC cohort study.

BACKGROUND: This study aims to establish a reliable prediction model of progressive fibrosing interstitial lung disease (PF-ILD) in patients with systemic sclerosis (SSc)-ILD, to achieve early risk stratification and to help better in preventing disease progression. METHODS: 304 SSc-ILD patients with no less than three pulmonary function tests within 6-24 months were included. We collected data at baseline and compared differences between SSc patients with and without PF-ILD. Least absolute shrinkage and selection operator regularisation regression and multivariable Cox regression were used to construct the prediction model, which were presented as nomogram and forest plot. RESULTS: Among the 304 patients with SSc-ILD included, 92.1% were women, with a baseline average age of 46.7 years. Based on the 28 variables preselected by comparison between SSc patients without PF-ILD group (n=150) and patients with SSc PF-ILD group (n=154), a 9-variable prediction model was constructed, including age≥50 years (HR 1.8221, p=0.001), hyperlipidemia (HR 4.0516, p<0.001), smoking history (HR 3.8130, p<0.001), diffused cutaneous SSc subtype (HR 1.9753, p<0.001), arthritis (HR 2.0008, p<0.001), shortness of breath (HR 2.0487, p=0.012), decreased serum immunoglobulin A level (HR 2.3900, p=0.002), positive anti-Scl-70 antibody (HR 1.9573, p=0.016) and usage of cyclophosphamide/mycophenolate mofetil (HR 0.4267, p<0.001). The concordance index after enhanced bootstrap resampling adjustment was 0.874, while the optimism-corrected Brier Score was 0.144 in internal validation. CONCLUSION: This study developed the first prediction model for PF-ILD in patients with SSc-ILD, and internal validation showed favourable accuracy and stability of the model.

Digital gangrene in systemic sclerosis patients: not only due to the microvascular disease.

OBJECTIVE: This study aims to investigate the characteristics, risk factors, and outcomes of digital gangrenes in SSc patients, and to identify whether vasculitis is one of the causes for digital gangrene. METHODS: A retrospective case-control study was performed from February 2003 to April 2021. Forty-three SSc patients with digital gangrene admitted to Peking Union Medical College Hospital were included. One-hundred forty-six age- and sex-matched SSc patients without gangrene were selected as controls during the same period. Univariate and multivariate logistic regression analysis was used to determine risk factors. RESULTS: Among 43 SSc patients with gangrene, 93.0% had Raynaud's phenomenon (RP) and 32.6% had current or previous digital ulcers (DU). SSc patients with digital gangrene had more ESR elevation (54.8% vs. 34.9%, p = 0.020) and higher level of high-sensitive C reactive protein (median 7.2 mg/L vs. 1.8 mg/L, p = 0.045) compared with controls. In the multivariable logistic regression analysis, smoking history (OR 4.119, p = 0.037), anti-centromere antibody positivity (OR 3.542, p = 0.016), anti-neutrophil cytoplasmic antibody positivity (OR 22.605, p = 0.037), and anti-phospholipid antibody positivity (OR 16.563, p = 0.001), as well as elevated ESR (OR 2.524, p = 0.038) were identified as independent risk factors for gangrenes. Most (79.1%) cases were treated with combination of immunosuppressive and vasodilating therapy, and four cases also got remised after treatment of only glucocorticoid and immunosuppressive agent. CONCLUSION: Smoking history; positive-ACA, ANCA, and anti-phospholipid antibodies; and increased ESR were independent risk factors for digital gangrenes in SSc. Vasculitis and macrovascular disease may contribute to the progression of digital gangrenes. Key Points •18.6% of SSc patients with digital gangrene had macrovascular stenosis. •Smoking, positive-ACA, ANCA, aPL, and increased ESR were indicators for digital gangrenes in SSc. •Vasculitis and macrovascular disease may involve in the pathogenesis.